Pasqualini Jorge Raul
Hormones and Cancer Research Unit, Paris, France.
Ann N Y Acad Sci. 2009 Feb;1155:88-98. doi: 10.1111/j.1749-6632.2009.04113.x.
Estrogen sulfotransferase is significantly more active in the normal breast cell (e.g., Human 7) than in the cancer cell (e.g., MCF-7). The data suggest that in breast cancer sulfoconjugated activity is carried out by another enzyme, the SULT1A, which acts at high concentration of the substrates. In breast cancer cells sulfotransferase (SULT) activity can be stimulated by various progestins: medrogestone, promegestone, and nomegestrol acetate, as well as by tibolone and its metabolites. SULT activities can also be controlled by other substances including phytoestrogens, celecoxib, flavonoids (e.g., quercetin, resveratrol), and isoflavones. SULT expression was localized in breast cancer cells, which can be stimulated by promegestone and correlated with the increase of the enzyme activity. The estrogen sulfotransferase (SULT1E1), which acts at nanomolar concentration of estradiol, can inactivate most of this hormone present in the normal breast; however, in the breast cancer cells, the sulfotransferase denoted as SULT1A1 is mainly present, and this acts at micromolar concentrations of E(2). A correlation was postulated among breast cancer cell proliferation, the effect of various progestins, and sulfotransferase stimulation. In conclusion, it is suggested that factors involved in the stimulation of the estrogen sulfotransferases could provide new possibilities for the treatment of patients with hormone-dependent breast and endometrial cancers.
雌激素磺基转移酶在正常乳腺细胞（如人7细胞）中的活性明显高于癌细胞（如MCF - 7细胞）。数据表明，在乳腺癌中，硫酸结合活性由另一种酶SULT1A进行，该酶在高浓度底物下起作用。在乳腺癌细胞中，磺基转移酶（SULT）活性可被多种孕激素刺激：甲地孕酮、普美孕酮和醋酸诺美孕酮，以及替勃龙及其代谢产物。SULT活性也可受其他物质控制，包括植物雌激素、塞来昔布、类黄酮（如槲皮素、白藜芦醇）和异黄酮。SULT表达定位于乳腺癌细胞中，可被普美孕酮刺激，并与酶活性增加相关。作用于纳摩尔浓度雌二醇的雌激素磺基转移酶（SULT1E1）可使正常乳腺中存在的大部分该激素失活；然而，在乳腺癌细胞中，主要存在的磺基转移酶为SULT1A1，它在微摩尔浓度的E(2)下起作用。推测乳腺癌细胞增殖、各种孕激素的作用与磺基转移酶刺激之间存在相关性。总之，有人提出，刺激雌激素磺基转移酶的相关因素可能为治疗激素依赖性乳腺癌和子宫内膜癌患者提供新的可能性。
